N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine has therapeutic utility in depressing blood glucose levels in the management of type 2 diabetes mellitus.
N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine is disclosed in Japanese Patent Application No. 63-54321 (equivalent to EP-A-196222 and U.S. Pat. No. 4,816,484). This Japanese application describes how the compound may be crystallized from aqueous methanol to yield crystals having a melting point of 129° C. to 130° C. These crystals are referred as “B-type”. These B-type crystals suffer from problems of instability, especially when subjected to mechanical grinding.
J. Med. Chem. 32, 1436 (1989) describes the preparation of N-(cyclohexylcarbonyl)-D-phenylalanines and related compounds, including N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine.
U.S. Pat. Nos. 5,463,116 and 5,488,150 describe the preparation of a novel crystalline form of N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine designated “H-type”. These patents also describe a method of treating form “B” crystals with appropriate solvent mixtures to obtain from “H” crystals and vice-versa. The H-type crystals have an enhanced stability over B type crystals.
Yaowu Fenxi Zazhi (2001), 21, 342 describes the “S” form of nateglinide as being different from form “B” and form “H”.